The autologous (or syngeneic) mixed lymphocyte reaction (AMLR) in mice is a measure of proliferation of Ly 1+23- T cells cultured with non-T cells from the same animal. The recognition event is mediated by cell surface antigens encoded in the I region of the major histocompatibility complex. This recognition event is associated with the development of suppressor cells which affect proliferative and cytotoxic responses of fresh T cells in mixed lymphocyte culture and also with helper cells which cause differentiation of cytotoxic T cells (CTC) recognizing hapten-modified self cell surface determinants. Finally, in the NZB mouse model, the extent of AMLR-related functional deficiencies is being determined along with investigation, both in vitro and in vivo, of the reversibility of any identified lesions. These latter studies will allow some conclusions regarding the potential of our findings for any therapeutic applications in humans.